Exploring undiagnosed celiac disease in women with recurrent reproductive failure: The gluten-free diet could improve reproductive outcomes

Am J Reprod Immunol. 2020 Feb;83(2):e13209. doi: 10.1111/aji.13209. Epub 2019 Nov 24.


Problem: Which is the prevalence and seroprevalence of celiac disease (CD) in women with recurrent reproductive failure?

Method of study: Retrospective study performed in a single infertility clinic from September 2016 to December 2017. A total of 690 women with unexplained history of recurrent miscarriage and/or recurrent implantation failure were consecutively recruited. IgA anti-transglutaminase 2 (TG2) antibody data were collected, as well as IgG anti-TG2 and IgA/IgG anti-deamidated gluten peptide (DGP) data in most cases, and IgG anti-gliadin antibodies occasionally. In selected women, HLA-DQ genotyping was requested. Biopsy was suggested to all women with positive serological results or belonging to CD risk groups. Reproductive outcomes were recorded from women with high suspicion of CD and a control group comprised of 49 women.

Results: Anti-TG2-positive women comprised 1% of the sample. An additional 4% was observed considering less-specific antibodies (31 women). Only 39% of sero-positive women accepted duodenal biopsy. HLA and biopsy data discarded CD in 14 sero-positive cases (37%), only one with anti-TG2 antibodies. CD was suggested in 10 sero-positive and three sero-negative women (1.9%). Compared with controls, the live birthrate of the studied women with probable CD was significantly decreased before gluten removal of the diet (P = .015), but significantly increased after that (P = .020).

Conclusion: One percent CD prevalence should be expected after anti-TG2 serological screening. However, more sensitive approaches should be explored, especially considering the potential beneficial effect of the gluten-free diet on the reproductive outcomes of women with CD.

Keywords: antibodies; celiac disease; celiac disease prevalence; embryo implantation; recurrent miscarriage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / etiology
  • Abortion, Habitual / prevention & control*
  • Adult
  • Antibody Specificity
  • Antigens / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Biopsy
  • Celiac Disease / complications*
  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology
  • Delayed Diagnosis
  • Diet, Gluten-Free*
  • Duodenum / pathology
  • Embryo Implantation, Delayed
  • Female
  • Fertilization in Vitro
  • GTP-Binding Proteins / immunology
  • Gliadin / immunology
  • HLA Antigens / genetics
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Live Birth
  • Middle Aged
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy Rate
  • Retrospective Studies
  • Transglutaminases / immunology


  • Antigens
  • Autoantibodies
  • Autoantigens
  • HLA Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • Gliadin
  • transglutaminase 2
  • Transglutaminases
  • GTP-Binding Proteins